Transcriptomics in Toxicogenomics, Part I: Experimental Design, Technologies, Publicly Available Data, and Regulatory...

Area of Science:

• Toxicology and Molecular Biology
• Environmental Health Sciences
• Biotechnology

Background:

• Conventional toxicity testing relies on phenotypic observations, but novel materials necessitate understanding molecular changes.
• Transcriptomics and toxicogenomics (TGx) offer detailed insights into biological responses to chemical and environmental agents.
• Standardization gaps in TGx data hinder its use in risk assessment.

Purpose of the Study:

• To review advancements in transcriptomic data generation and analysis for toxicogenomics.
• To provide guidelines for experimental design, data handling, and resource utilization in TGx.
• To discuss the integration of TGx into regulatory frameworks and the 3R concept.

Main Methods:

• Review of DNA microarray, RNA sequencing (RNA-Seq), and single-cell RNA-Seq (scRNA-Seq) methodologies.
• Summarization of guidelines for exposure parameters, endpoint selection, and sample handling.
• Compilation of publicly available TGx data resources.

Main Results:

• Recent advancements in transcriptomic technologies (microarray, RNA-Seq, scRNA-Seq) are summarized.
• Guidelines for robust experimental design, including exposure, dose, endpoints, and sample quality, are presented.
• Publicly available TGx data resources and their applications in toxicity prediction are highlighted.

Conclusions:

• Standardized TGx methods, adhering to FAIR principles, are essential for robust risk assessment.
• Implementing TGx supports alternative testing strategies and the 3R concept in animal research.
• This review provides foundational knowledge for subsequent articles on TGx data preprocessing and modeling.